Benzhydrocodone, also known as benzoate-hydrocodone, is an opioid prodrug of the morphinan class and having the following chemical structure:
                (hydrocodone coupled with benzoic acid).        
Benzhydrocodone itself is inactive, but acts as a prodrug, producing hydrocodone upon cleavage of the benzoate portion of the molecule. Benzhydrocodone was designed to be an opioid analgesic with lower abuse potential.
SCHOFP, C., in U.S. Pat. No. 1,731,152, issued Oct. 8, 1929 describes a process for the manufacture of a derivative of dihydrocodeinone or its substitution products, including preparation of methiodide of benzoyl hydrocodeinone.
SMALL, L. et al., in Journal of Organic Chemistry, 1938, p. 204. Vol. 3 describes a process for the preparation of hydrocodone enol acetate by reacting hydrocodone with acetic anhydride in the presence of sodium acetate and heat.
LIKHOTVORIK, I., et al., in U.S. Pat. No. 7,348,430, issued Mar. 25, 2008, describe a process for the manufacture of dihydrothebaine, dihydrocodeinone enol acetate, hydrocodone, and analogs.
MICKLE, T., et al., in U.S. Pat. No. 8,461,137, issued Jun. 11, 2013, MICKLE, T., et al., in U.S. Pat. No. 8,748,413, issued Jun. 10, 2014, and MICKLE, T., et al., in U.S. Pat. No. 8,759,368, issued Jun. 24, 2014, describe compositions comprising aryl carboxylic acids chemically conjugated with hydrocodone to form prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids.
HEINRICH, B. W., et al., in PCT Patent Publication WO 2014/138740 A1, published Sep. 12, 2014 (US Equivalent Patent Publication US 2016/0039837), describe pharmaceutically acceptable salts and polymorphic forms of hydrocodone benzoic acid enol ester and processes for making same.
There remains a need for a process for the preparation of benzhydrocodone hydrochloride that is suitable for large scale and/or commercial manufacture.